| Literature DB >> 29136503 |
Hugues de Thé1, Pier Paolo Pandolfi2, Zhu Chen3.
Abstract
Recent clinical trials have demonstrated that the immense majority of acute promyelocytic leukemia (APL) patients can be definitively cured by the combination of two targeted therapies: retinoic acid (RA) and arsenic. Mouse models have provided unexpected insights into the mechanisms involved. Restoration of PML nuclear bodies upon RA- and/or arsenic-initiated PML/RARA degradation is essential, while RA-triggered transcriptional activation is dispensable for APL eradication. Mutations of the arsenic-binding site of PML/RARA, but also PML, have been detected in therapy-resistant patients, demonstrating the key role of PML in APL cure. PML nuclear bodies are druggable and could be harnessed in other conditions.Entities:
Keywords: PML; RARA; SUMO; arsenic; differentiation; mouse models; precision medicine; retinoic acid; targeted therapy
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Year: 2017 PMID： 29136503 DOI： 10.1016/j.ccell.2017.10.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743